Beware of hepatocellular carcinoma in HIV-infected patients !

Clinical History

A middle-aged male with a long-standing history of human immunodeficiency virus (HIV) and chronic hepatitis C virus (HCV)-related liver disease presented to our department. Until recently the patient was in in acceptable clinical and immunological (CD4+ count 135 cells/mmc, suppressed viral load) condition on combined antiretroviral therapy, and now manifests with sudden liver failure with jaundice and ascites.

Discussion

During the last two decades, antiretroviral therapy dramatically changed the natural history and outcome of Human Immunodeficiency Virus (HIV)-infected people by suppressing HIV, improving immune function, decreasing opportunistic infections and Acquired Immunodeficiency Syndrome (AIDS)-defining cancers, and ultimately resulted in increased survival with better quality of life. However, in patients with long-standing HIV disease the combination of increased lifespan, prolonged exposure to environmental and lifestyle cancer risk factors, and coinfection with oncogenic viruses progressively led to the emergence of several non-AIDS-defining neoplasms such as squamocellular anal carcinoma, Hodgkin lymphoma, lung and colorectal cancers, melanoma and basal cell skin tumours [1-7].Because of shared transmission route, coinfection with hepatitis C virus (HCV) is very common (almost 30%): HIV+HCV coinfection is present in two-thirds of patients with cirrhosis and represents the key risk factor for developing HCC along with increasing age and low CD4 cell count. As a result, cirrhosis, end-stage liver disease and hepatocellular carcinoma (HCC) currently represent the leading (approximately 50%) cause of mortality [1-7].Albeit the mechanisms of accelerated hepatocarcinogenesis are still unclear, HCC represents a growing concern in HIV-positive individuals, with a 4-fold increased risk compared to the general population and 6.72 cases/1000 person-years incidence rate. Compared to non-HIV cohorts, HIV-positive patients with HCC are younger, more likely males, with fewer comorbidities [3-5, 8-10].Imaging surveillance is crucial to allow HCC detection at an early stage and timely treatment with chemoembolization, biological drugs and liver transplantation: the latter is feasible, without differences in outcome and recurrence rates compared to non-HIV patients [11]. In the HIV setting the otherwise rare infiltrative growth pattern and portal obstructing tumour are relatively common (23-30% of cases): HCC is often challenging to discern from the markedly heterogeneous cirrhotic background not only sonographically but also at cross-sectional CT and MR imaging. Albeit permeative growth and hypovascularity cause decreased conspicuity on dynamic contrast-enhanced studies, aware radiologists should suspect HCC when faced with irregular, heterogeneous venous- and equilibrium-phase hypoattenuation compared to the remaining parenchyma, despite inconsistent arterial enhancement. Conversely, the true extent of the tumour is generally best assessed on unenhanced T1-, T2- and diffusion-weighted MR images. The presence of expansile or vascularised portal thrombus represents a red-flag sign [12-14]Despite younger age, median survival is shorter (grossly half, 40% one-year survival) than that of non-HIV counterparts. Adverse prognostic factors include advanced HCC stage, tumour size over 3 cm, diagnosis outside screening program, and portal thrombosis [2-4, 7, 10].